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Neostigmine treatment induces neuroprotection against oxidative stress in cerebral cortex of asthmatic mice

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Abstract

During chronic inflammatory disease, such asthma, leukocytes can invade the central nervous system (CNS) and together with CNS-resident cells, generate excessive reactive oxygen species (ROS) production as well as disbalance in the antioxidant system, causing oxidative stress, which contributes a large part to neuroinflammation. In this sense, the aim of this study is to investigate the effects of treatment with neostigmine, known for the ability to control lung inflammation, on oxidative stress in the cerebral cortex of asthmatic mice. Female BALB/cJ mice were submitted to asthma model induced by ovalbumin (OVA). Control group received only Dulbecco’s phosphate-buffered saline (DPBS). To evaluate neostigmine effects, mice received 80 μg/kg of neostigmine intraperitoneally 30 min after each OVA challenge. Our results revealed for the first time that treatment with neostigmine (an acetylcholinesterase inhibitor that no crosses the BBB) was able to revert ROS production and change anti-oxidant enzyme catalase in the cerebral cortex in asthmatic mice. These results support the communication between the peripheral immune system and the CNS and suggest that acetylcholinesterase inhibitors, such as neostigmine, should be further studied as possible therapeutic strategies for neuroprotection in asthma.

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Acknowledgements

This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil.

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Authors and Affiliations

  1. Laboratory of Pediatric Respirology, Infant Center, School of Medical, Pontifical Catholic University of Rio Grande do Sul, PUCRS, Porto Alegre, Brazil

    Géssica Luana Antunes, Josiane Silva Silveira, Daniela Benvenutti Kaiber, Carolina Luft, Renato Tetelbom Stein & Aline Andrea da Cunha

  2. Laboratory of Neuroprotection and Metabolic Disease, Department of Biochemistry, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil

    Tiago Marcon dos Santos, Eduardo Peil Marques, Fernanda Silva Ferreira, Felipe Schmitz & Angela Terezinha de Souza Wyse

  3. Infant Center, Institutional Research Coordinator, Pontifical Catholic University of Rio Grande do Sul - PUCRS, Hospital Moinhos de Vento, Porto Alegre, Brazil

    Paulo Márcio Pitrez

Authors
  1. Géssica Luana Antunes
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  2. Josiane Silva Silveira
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  3. Daniela Benvenutti Kaiber
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  4. Carolina Luft
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  5. Tiago Marcon dos Santos
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  6. Eduardo Peil Marques
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  7. Fernanda Silva Ferreira
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  8. Felipe Schmitz
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  9. Angela Terezinha de Souza Wyse
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  10. Renato Tetelbom Stein
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  11. Paulo Márcio Pitrez
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  12. Aline Andrea da Cunha
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Corresponding author

Correspondence to Aline Andrea da Cunha.

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The authors declare that they have no conflict of interest.

Ethical approval

The experiments were conducted in accordance with the Brazilian Society of Laboratory Animal Science (SBCAL), using fewer animals and adequate management of pain and suffering, during the study procedures and euthanasia. This study was approved by the Ethics Committee for the Use of Animals of the Pontifical Catholic University of Rio Grande do Sul (CEUA, 7934).

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Antunes, G.L., Silveira, J.S., Kaiber, D.B. et al. Neostigmine treatment induces neuroprotection against oxidative stress in cerebral cortex of asthmatic mice. Metab Brain Dis 35, 765–774 (2020). https://doi.org/10.1007/s11011-020-00558-7

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